1. Field of the Invention
The present invention relates to a human endothelin receptor, DNA sequence encoding the receptor, an expression vector carrying the DNA sequence, a transformant comprising the expression vector, and a method for producing a human endothelin receptor from the transformant.
2. Description of the Prior Art
An endothelin receptor (ET-receptor) is a receptor for an endothelin (ET). ET-receptors derived from animals such as bovines and rats have been known. An ET is a peptide present in various tissues in animals and is known as a strong vasoconstrictor. Cloning and sequence analysis of known ET genes have revealed that the ETs comprise three kinds of isopeptides: Endothelin 1 (ET-1), Endothelin 2 (ET-2), and Endothelin 3 (ET-3). Thereafter, it has been found that these ETs are distributed in a wide variety of vascular and non-vascular tissues (Proc. Natl. Acad. Sci. C.S.A. 86, 2863-2867 (1989); Trends in Pharmacol. Sci. 10, 374-378 (1989); and Proc. Natl. Acad. Sci. U.S.A. 87, 2359-2363 (1990)). ET-1 has initially been identified as a strong vasoconstrictive peptide with 21-amino-acid residues produced by porcine vascular endothelial cells (Nature, 332, 411-415 (1988)).
It has previously been shown in vivo that ET-1 and ET-2 are much more strong vasoconstrictors than ET-3, whereas the three ET isopeptides are roughly equipotent in producing the transient vasodilation.
As described above, the analysis of nucleic acid sequences of ETs has revealed that various kinds of ET isopeptides exist. These ET isopeptides are also different in their properties. Therefore, it appears that various subtypes of ET-receptors exist. The existence of various subtypes of ET-receptors has been proved by the radioactive ligand binding studies of Watanabe, H. et al. (Biochem. Biophys. Res. Commun., 161, 1252-1259 (1989)), and Martin, E. R. et al. (J. Biol. Chem. 265, 14044-14049 (1990)). These studies indicate the existence of, at least, two kinds of ET-receptors. One of them has a higher affinity for ET-1 and ET-2 than for ET-3; and the other has an affinity for ET-1, ET-2, and ET-3 with no selectivity.
The ET-receptor is useful as a reagent for measuring the amount of ET or useful in screening for an antagonist of the ET-receptor so as to study agents for the circulatory system. Therefore, there is a demand for a structure analysis of the ET-receptor and effective production of the ET-receptor by means of genetic engineering using the information of this structural analysis.